Ultrasound for diagnosing acute salpingitis: a prospective observational diagnostic study

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1 Human Reproduction, Vol.28, No.6 pp , 2013 Advanced Access publication on March 15, 2013 doi: /humrep/det065 ORIGINAL ARTICLE Gynaecology Ultrasound for diagnosing acute salpingitis: a prospective observational diagnostic study G. Romosan 1, *, C. Bjartling 1, L. Skoog 2, and L. Valentin 1 1 Department of Obstetrics and Gynaecology, Skåne University Hospital Malmö, Lund University, Malmö , Sweden 2 Department of Clinical Pathology Malmö, Laboratory Medicine, Malmö , Sweden *Correspondence address. Tel: ; Fax: ; gina.romosan@gmail.com Submitted on October 31, 2012; resubmitted on January 8, 2013; accepted on February 18, 2013 study question: What are the diagnostic benefits of using ultrasound in patients with a clinical suspicion of acute salpingitis and signs of pelvic inflammatory disease (PID)? summary answer: In patients with a clinical suspicion of acute salpingitis, the absence of bilateral adnexal masses at ultrasound decreases the odds of mild-to-severe acute salpingitis about five times, while the presence of bilateral adnexal masses increases the odds about five times. what is known already: PID is difficult to diagnose because the symptoms are often subtle and mild. The diagnosis is usually based on clinical findings, and these are unspecific. The sensitivity and specificity of ultrasound with regard to salpingitis have been reported in one study (n ¼ 30) of appropriate design, where most patients had severe salpingitis (i.e. pyosalpinx) or tubo-ovarian abscess. study design, size, duration: This diagnostic test study included 52 patients fulfilling the clinical criteria of PID. Patients were recruited between October 1999 and August participants/materials, setting, methods: The patients underwent a standardized transvaginal gray scale and Doppler ultrasound examination by one experienced sonologist (index test) before diagnostic laparoscopy by a laparoscopist blinded to the ultrasound results. The final diagnosis was determined by laparoscopy, histology of the endometrium and other histology where relevant (reference standard). main results and the role of chance: Of the 52 patients, 23 (44%) had a final diagnosis unrelated to genital infection, while the other 29 had cervicitis (n ¼ 3), endometritis (n ¼ 9) or salpingitis (n ¼ 17; mild n ¼ 4, moderate n ¼ 8, severe, i.e. pyosalpinx n ¼ 5). Bilateral adnexal masses and bilateral masses lying adjacent to the ovary were seen more often on ultrasound in patients with salpingitis than with other diagnoses (bilateral adnexal masses: 82 versus 17%, i.e. 14/17 versus 6/35, P ¼ 0.000, positive likelihood ratio 4.8, negative likelihood ratio 0.22; bilateral masses adjacent to ovary: 65 versus 17%, i.e.11/17 versus 6/35, P ¼ 0.001, positive likelihood ratio 3.8, negative likelihood ratio 0.42). In cases of salpingitis, the masses lying adjacent to the ovaries were on average 2 3 cm in diameter, solid (n ¼ 14), unilocular cystic (n ¼ 4), multilocular cystic (n ¼ 3) or multilocular solid (n ¼ 1), with thick walls and well vascularized at colour Doppler. In no case were the cogwheel sign or incomplete septae seen. All 13 cases of moderate or severe salpingitis were diagnosed with ultrasound (detection rate 100%, 95% confidence interval %) compared with 1 of 4 cases of mild salpingitis. Three of six cases of appendicitis, and two of two ovarian cysts were correctly diagnosed with ultrasound, and one case of adnexal torsion was suspected and then verified at laparoscopy. limitations, reasons for caution: The sample size is small. This is explained by difficulties with patient recruitment. There are few cases of mild salpingitis, which means that we cannot estimate with any precision the ability of ultrasound to detect very early salpingitis. The proportion of cases with salpingitis of different grade affects the sensitivity and specificity of ultrasound, and the sensitivity and specificity that we report here are applicable only to patient populations similar to ours. wider implications of the findings: The information provided by transvaginal ultrasound is likely to be of help when deciding whether or not to proceed with diagnostic laparoscopy in patients with symptoms and signs suggesting PID and, if laparoscopy is not performed, to select treatment and plan follow-up. & The Author Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please journals.permissions@oup.com

2 1570 Romosan et al. study funding/competing interest(s): This work was supported by funds administered by Malmö University Hospital and two Swedish governmental grants (ALF-medel and Landstingsfinansierad Regional Forskning). The authors have no conflict of interest. Key words: salpingitis / ultrasonography / Doppler ultrasonography / emergency medicine / sensitivity/specificity Introduction Pelvic inflammatory disease (PID) is difficult to diagnose because the symptoms are often subtle and mild. Because there are no precise tests for PID, a diagnosis is usually based on clinical findings, but clinical diagnosis of PID is hampered by the lack of specificity of signs and symptoms. On physical examination, pelvic and abdominal tenderness, abnormal cervical secretions and fever are findings associated with PID (CDC, 2010). However, in a study by Jacobson and Westrom (1969), only 65% of patients with a clinical diagnosis of PID had salpingitis confirmed when laparoscopy was performed, 23% had normal findings and in the remaining 12% laparoscopy revealed pathologic conditions unrelated to PID (acute appendicitis, ectopic pregnancy, pelvic endometriosis and several other pelvic disorders) (Jacobson and Westrom, 1969). Palpable adnexal fullness or mass is a common finding in women with salpingitis and is related to the severity of inflammation as determined by laparoscopy. However, palpable adnexal fullness or mass is also reported in some women with normal findings on laparoscopy (Jacobson and Westrom, 1969). Transvaginal ultrasound has become increasingly common as an aid to establish a correct diagnosis in women with acute pelvic pain (Okaro and Valentin, 2004). Ultrasound findings suggestive of pyosalpinx have been described, i.e. a pear-shaped fluid-filled structure with thick walls, presence of incomplete septae and cogwheel sign (Timor- Tritsch et al., 1998). Moreover, increased vascularisation as determined by Doppler ultrasound has been reported in cases of inflammation-induced hyperemia in the tubes (Alatas et al., 1996; Molander et al., 2001). The aim of this study was to (i) describe ultrasound findings in cases of acute mild, moderate and severe salpingitis verified by laparoscopy and (ii) to estimate the sensitivity and specificity of transvaginal ultrasound for diagnosing acute salpingitis in patients with clinical signs of PID. Methods This is a prospective observational study. Consecutive patients scheduled for diagnostic laparoscopy at the department of Obstetrics and Gynaecology, Skåne University Hospital, Malmö, Sweden, because of a clinical suspicion of acute salpingitis were eligible for inclusion. The clinical examination in the emergency room upon which the doctor based his/ her clinical diagnosis included speculum examination, wet smear and gynaecological palpation. Presenting symptoms and clinical findings were documented prospectively in a research protocol by the doctor in the emergency room. In addition, blood was drawn for analysis of C-reactive protein (CRP) and body temperature was measured. Salpingitis was suspected if the following criteria were fulfilled: acute abdominal pain for 1 14 days, cervical motion tenderness and adnexal tenderness at pelvic bimanual examination, negative pregnancy test and at least one of the following three signs: pathological saline prepared vaginal wet smear (more leucocytes than epithelial cells in the absence of clue-cells and inflammatory vaginitis) or pathological discharge at speculum examination, elevated CRP, oral temperature.38.08c. These criteria are similar to the criteria of PID of the Centers for disease control and prevention, USA (CDC, 2010). According to both the policy of our department and our research protocol, all patients fulfilling these criteria should undergo diagnostic laparoscopy. Tests for Neisseria gonorrhoeae (N. gonorrhoeae) and Chlamydia trachomatis (C. trachomatis) were performed. Neisseria gonorrhoeae was detected by culture from a charcoal-treated cotton swab which was sent to the laboratory in Stuart s transport medium. First void urine together with cervical samples, or vaginal swabs together with urine, were collected to diagnose C. trachomatis using PCR (Roche Molecular Diagnostics, Pleasanton, CA, USA, or m2000, Abbott Molecular, Inc., Des Plaines, IL, USA). Our inclusion criteria were age 18 years (the age of legal consent), signed informed consent, no unequivocal alternative diagnosis to PID on the basis of clinical evaluation and no ongoing treatment with antibiotics or anti-inflammatory drugs, but antibiotic therapy started,24 h before the laparoscopy was accepted. Exclusion criteria were violation of the study protocol or treatment with antibiotics.24 h before laparoscopy. After a decision to perform laparoscopy had been taken by the physician in the emergency room, and after the patient had consented to participate in the study, a standardized transvaginal gray scale and colour and spectral Doppler ultrasound examination was performed by a gynaecologist with more than 10 years of experience in gynecological ultrasound (LV). The ultrasound examiner knew that the eligibility criteria of the study were fulfilled but did not have access to any other clinical information. The ultrasound system used was a Sequoia 512 (Siemens Medical Solutions, Inc., Ultrasound Division, Mountain View, CA, USA) equipped with a 5 8 MHz transvaginal transducer. All women were examined in the lithotomy position with an empty bladder. The uterus and adnexa were scanned systematically following the research protocol. The presence/absence of fluid in the endometrial cavity, the cervical canal and the pouch of Douglas was noted. The ovaries were described with regard to the presence of corpus luteum, polycystic appearance and any pathological intra-ovarian lesions. Any adnexal lesions were noted, and the gray scale morphology of any such lesion was described using the terminology of the International Ovarian Tumor Analysis group (Timmerman et al., 2000). Subjective assessment, i.e. pattern recognition was also used for evaluation of ultrasound findings (Valentin, 1999; Valentin, 2004) with ultrasound signs reported to be specific for pyosalpinx (Timor-Tritsch et al., 1998, Valentin, 2004) being searched for. Three orthogonal diameters of any mass were measured. We report the size of masses as the mean of three orthogonal diameters. The dynamic and interactive nature of transvaginal ultrasound was made full use of for pain mapping and for estimating the mobility of organs and lesions. After the gray scale ultrasound examination had been completed, the ultrasound system was switched into the colour Doppler mode, and the colour content of the endometrium, myometrium and any adnexal mass suspected to be a diseased tube was estimated subjectively by the ultrasound examiner on a visual analog scale graded from 0 to 100. Standardized colour Doppler settings were used (frequency 6 MHz; power Doppler gain 50; dynamic range 10 db; edge 1; persistence 2; colour map 1; gate 2; filter 3). Finally, blood flow velocities were measured in the uterine

3 Ultrasound for diagnosing acute salpingitis 1571 arteries, in the tubal arteries at the place where the tube leaves the uterus (Kirchler et al., 1992) and in the wall of any adnexal mass. Angle correction was used when measuring blood flow velocities in the uterine arteries. For the other vessels angle correction was not used, but the highest achievable Doppler shift signals were sought for each vessel (Valentin et al., 1994). Ultrasound images were documented on hard copies, on video tape or electronically. Based on the subjective evaluation of the ultrasound findings, the ultrasound examiner suggested a likely diagnosis. The ultrasound results were entered into a research protocol. The ultrasound examiner played no role in the clinical management of the patient, and all staff managing the patient including the laparoscopist was blinded to the ultrasound results. After the ultrasound examination, laparoscopy was performed by gynaecologists with different levels of expertise (senior registrar or consultant). Immediately before the laparoscopy with the patient anaesthetizsed, any intrauterine contraceptive device was removed, and an endometrial sample was taken using both an Endorette TM outpatient endometrial sampling device (Medscand AB, Malmö, Sweden) and a currette. The Endorette is a sterile device with a polyethylene piston which slides within a straight but flexible polypropylene sheath with four lateral holes near its tip. Its length is 285 mm and its outer diameter is 2.6 mm. The endometrial samples were analyzed by one dedicated pathologist (L.S.) with the specific aim of confirming or excluding endometritis. At laparoscopy, cultures were taken from the tubal fimbriae and from fluid in the pouch of Douglas for analysis of C. trachomatis and N. gonorrhoeae. The laparoscopy was documented on video tape or on DVD. Immediately after the laparoscopy, the laparoscopist described the laparoscopic findings in a standardized research protocol. The final diagnosis was determined by the authors on the basis of the results of endometrial histology and findings at laparoscopy. A diagnosis of acute salpingitis was made if the laparoscopic criteria of mild, moderate or severe salpingitis as suggested by Hager et al. (1983) were fulfilled. The minimal criteria for a diagnosis of salpingitis were tubal redness, tubal edema and pus or exudate from the tubal fimbriae provoked by manipulation (salpingitis grade 1, i.e. mild salpingitis). If, in addition to the minimal criteria, pus was present spontaneously and the tubes were fixed and closed, we classified the condition as salpingitis grade 2 (i.e. moderate salpingitis). If there was a pyosalpinx or a tubo-ovarian abscess, the condition was classified as salpingitis grade 3 (i.e. severe salpingitis) (Hager et al., 1983). The diagnosis of endometritis was made when there were neutrophlic microabscesses plus infiltration and destruction of glandular epithelium in the endometrial sample (acute endometritis) or infiltration of plasma cells, histiocytes, lymphocytes and lymphoid follicles (chronic endometritis) or both but no signs of salpingitis at laparoscopy (Sellors et al., 1991; Blaustein and Kurman, 2002). A final diagnosis of cervicitis was made if there were clinical signs of cervicitis but neither the criteria of endometritis nor those of salpingitis were fulfilled. We collected information regarding parity, gynecological history and use of contraceptives from the patient records retrospectively. Statistical analysis Statistical calculations were undertaken using the Statistical Package for the Social Sciences (SPSS, Inc., Chicago, Illinois, USA, version 16.0 or 17.0). The statistical significance of a difference in unpaired proportions was determined using the x 2 test or Fisher s exact test as appropriate, and the statistical significance of a difference in continuous unpaired data was determined using the Mann Whitney test. Exact 95% confidence intervals (CI) for sensitivity and specificity were calculated. When the sensitivity was 100%, positive and negative likelihood ratios were calculated by adding 0.5 to all four fields in the four-field table. A P-value,0.05 was considered statistically significant. Ethical approval The Ethics Committee of Lund University, Sweden, approved the study protocol. Written informed consent was obtained from all participants, after the nature of the procedures had been fully explained. Results Recruitment was from October 1999 until August A total of 85 patients scheduled for diagnostic laparoscopy because of a clinical suspicion of salpingitis consented to be included in the study, but 33 had to be excluded: 5 because they were treated with antibiotics for.48 h before the laparoscopy, 1 because the laparoscopy was carried out 13 days after the ultrasound examination, 11 because the planned laparoscopy was cancelled and 16 because the ultrasound examiner was not available to perform the scan before the laparoscopy. Thus, 52 patients were included. Of the 52 patients included, 8 received antibiotics during the 24 h preceding the ultrasound examination and the laparoscopy (three cases with a final diagnosis of salpingitis or pyosalpinx and five cases with a final diagnosis of pelvic pain with unknown etiology). The median time between the ultrasound examination and the diagnostic laparoscopy was 4.9 h (range 0.5 to 48 h). The final diagnosis of the 52 patients included was salpingitis (17/ 52, 32.7%), endometritis (9/52, 17.3%), cervicitis (3/52, 5.8%) and other (23/52, 44.2%). Four of the 17 cases of salpingitis were mild, 8 were moderate and 5 were severe (i.e. pyosalpinx). No patient had a tubo-ovarian abscess. The other diagnoses were pelvic pain with unknown etiology (7/52, 13.5%), appendicitis (6/52, 11.5%), peritoneal or ovarian endometriosis (2/52, 3.8%), ovarian cyst (2/52, 3.8%), urinary tract infection (2/52, 3.8%), adnexal torsion (2/52, 3.8%), i.e. one case of torsion of a hydrosalpinx and one of torsion of a Morgagni hydatid, mucinous cystadenocarcinoma in the appendix (1/52, 1.9%) and Crohn s disease (1/52, 1.9%). Demographic background data, symptoms, findings at clinical examination, results of cultures/pcr and endometrial histology are shown in Table I. No patient was diagnosed with N. gonorrhoeae. More patients with salpingitis and endometritis than with other diagnoses complained of discharge (17/25 versus 8/26, P ¼ 0.012), but there were no other obvious differences in either demographic background data, symptoms or clinical findings between women with laparoscopically confirmed salpingitis and those with other diagnoses. Patients with salpingitis had the highest CRP values (median 75, range versus 42, 8 374, P ¼ 0.016). Some ultrasound results are shown in Tables II and III. There was no obvious difference in the presence of or the amount of fluid in the pouch of Douglas between patients with salpingitis, endometritis and other diagnoses. Polycystic appearance of the ovaries was not more common in patients with salpingitis than in other patients. Bilateral adnexal masses and bilateral adnexal masses lying adjacent to the ovary were seen more often at ultrasound examination in patients with salpingitis than with other diagnoses (14/17 versus 6/35, P ¼ 0.000; 11/17 versus 6/35, P ¼ 0.001). The colour score of the endometrium was highest in patients with endometritis, while pulsatility index (PI) values were lowest and time averaged maximum velocities (TAMXV) were highest in the uterine and tubal

4 1572 Romosan et al. Table I Demographic background data, symptoms and findings at clinical examination. Final diagnosis... Salpingitis Endometritis Cervicitis Others a Total (n 5 52) (n 5 17) (n 5 9) (n 5 3) (n 5 23)... Hours between scan and laparoscopy 4.7 (0.5 48) 3.7 (1.5 24) 6.2 (2 8) 6.4 (1 48) 4.9 (0.5 48) Antibiotic treatment before laparoscopy b 3/17 (17.6) 0/9 0/3 5/23 (21.7) 8/52 (15.4) Age (years) 28 (20 50) 27 (21 30) 27 (20 28) 28 (17 48) 28 (17 50) Nullipara 7/17 (41.2) 6/9 (66.7) 2/3 (66.7) 10/23 (43.5) 25/52 (48.1) Current IUD 4/17 (23.5) 2/9 (22.2) 1/3 (33.3) 7/23 (30.4) 14/52 (26.9) Current contraceptive pill 6/17 (35.3) 2/7 (28.6) 1/3 (33.3) 7/22 (31.8) 16/49 (32.7) Previous salpingitis 2/17 (11.8) 0/8 0/3 2/21 (9.5) 4/49 (8.2) Previous ectopic pregnancy 1/17(5.9) 0/9 0/3 0/23 1/52 (1.9) Undergone appendectomy 0/17 1/8 (12.5) 1/3 (33.3) 2/23 (8.7) 4/51 (7.8) Symptoms Pelvic pain 17/17 (100) 9/9 (100) 3/3 (100) 23/23 (100) 52/52 (100) Discharge 11/16 (68.8) 6/9 (66.7) 1/3 (33.3) 7/23 (30.4) 25/52 (48.1) Bleeding 6/17 (35.3) 3/9 (33.3) 1/3 (33.3) 2/23 (8.7) 12/52 (23.1) Clinical findings General condition affected 9/16 (56.2) 7/9 (77.8) 2/2 (100) 18/23 (78.3) 36/50 (72.0) Pathological discharge at speculum 12/17 (70.6) 9/9 (100) 3/3 (100) 19/23(83.6) 43/52 (82.7) examination Cervical tenderness 12/16 (75.0) 7/9 (77.8) 1/3 (33.3) 15/21 (71.4) 35/49 (71.4) Uterine tenderness 14/17 (82.4) 9/9 (100) 3/3 (100) 20/23 (87.0) 46/52 (88.5) Adnexal tenderness Unilateral 3/17 (17.6) 1/9 (11.1) 3/3 (100) 10/23 (43.5) 17/52 (32.7) Bilateral 14/17 (82.4) 8/9 (88.9) 0/3 13/23 (56.5) 35/52 (67.3) Palpable pelvic mass 6/16 (37.5) 1/9 (11.1) 2/3 (66.7) 2/23 (8.7) 11/51 (21.6) Temperature 38 C8 10/17 (58.8) 2/9 (22.2) 1/3 (33.3) 11/23 (47.8) 24/52 (46.2) CRP.8 17/17 (100) 7/9 (77.7) 2/3 (66.7) 20/23 (87.0) 46/52 (88.4) CRP 75 (15 204) 42 (8 145) 10 (8 47) 51 (8 374) 52 (8 374) Chlamydia trachomatis positive c 6/17 (35.3) 2/9 (22.2) 0/3 0/22 8/51 (15.4) Neisseria gonorrhoeae positive c 0/13 0/7 0/0 0/16 0/36 Endometrial histology compatible with 11/16 (68.8) d 9/9 (100) 0/2 e 0/20 f 20/47 (42.6) endometritis Results are shown as the median (range) or n (%). IUD, intrauterine device; CRP, C-reactive protein. a Pelvic pain with unknown etiology (n ¼ 7), appendicitis (n ¼ 6), peritoneal endometriosis (n ¼ 2), ovarian cyst (n ¼ 2), adnexal torsion (n ¼ 2), urinary tract infection (n ¼ 2), Crohn s disease (n ¼ 1), cystadenocarcinoma of the appendix (n ¼ 1). b Always,24 h before laparoscopy. c Positive in cervix, urine or abdominal fluid. d In one case no endometrial sampling was performed, in two cases the endometrial biopsy yielded insufficient material, in three cases there were no signs of endometritis in the endometrial sample but the laparoscopy findings clearly fulfilled the criteria of salpingitis (mild in two cases and moderate in one case). e In one case endometrial sampling was not performed. f In three cases endometrial sampling was not performed. arteries in patients with salpingitis. However, there was substantial overlap in Doppler results between patients with different diagnoses. The diagnoses suggested by the ultrasound examiner are shown in Table IV. The sensitivity with regard to acute salpingitis of subjective interpretation of the ultrasound findings by the ultrasound examiner was 82% (14/17, 95% CI 57 96%), the specificity was 77% (27/35, 95% CI 60 90%), the positive likelihood ratio was 3.6 and the negative likelihood ratio was The sensitivity and specificity of ultrasound findings of bilateral masses lying adjacent to the ovary were 65% (11/17, 95% CI 38 86%) and 83% (29/35, 95% CI 66 93%), and the positive and negative likelihood ratios were 3.8 and 0.42, respectively. The corresponding figures for bilateral adnexal masses were 82% (14/17, 95% CI 57 96%), 83% (29/35, 95% CI 66 93%), 4.8 and Bilateral adnexal masses were found in all 13 patients with moderate or severe salpingitis but in only one of four patients with mild salpingitis. Thus, the sensitivity and specificity

5 Ultrasound for diagnosing acute salpingitis 1573 Table II Characteristics of ultrasound examination and ultrasound findings. Final diagnosis... Salpingitis (n 5 17) Endometritis (n 5 9) Others a (n 5 26) Total (n 5 52)... Cycle day 14.8 (2 35) 19.7 (1 37) 16.6 (2 60) b 16.6 (1 60) Fluid in the Cervical canal 3/17 (17.2) 5/9 (55.6) 2/25 (8.0) 10/51 (19.6) Endometrial cavity 5/17 (29.4) 3/9 (33.3) 0/26 8/52 (15.4) Pouch of Douglas 14/17 (82.4) 7/9 (77.8) 16/26 (61.5) 37/52 (71.2) Amount of fluid in the pouch of Douglas (mm) 10.0 (0 22) 8.8 (0 21) 8.5 (0 29) 9.0 (0 29) Polycystic appearance of ovary c Right ovary 4/15 (26.7) 2/9 (22.2) 5/26 (19.2) 11/50 (22.0) Left ovary 2/15 (13.3) 3/8 (37.5) 1/24 (4.2) 6/47 (12.8) Bilateral masses adjacent to the ovary 11/17 (64.7) 3/9 (33.3) 3/26 (11.5) 17/52 (38.5) Bilateral adnexal masses 14/17 (82.4) 3/9 (33.3) 3/26 (11.5) 20/52 (38.5) Unilateral mass adjacent to the ovary 0/17 0/9 6/26 (23.1) 6/52 (11.5) Unilateral ovarian cyst 0/17 0/9 2/26 (7.7) 2/52 (3.8) No adnexal mass 3/17 (17.6) 6/9 (66.6) 15/26 (57.7) 24/52 (46.2) Bilateral masses adjacent to the ovary Both with colour score 70 5/10 (50) d 1/2 (50) e 1/3 (33.3) 7/15 (46.7) One with colour score 70 1/10 (10) d 0/2 e 2/3 (77.8) 3/15 (20) None with colour score 70 4/10 (40) d 1/2 (50) e 0/3 5/15 (33.3) Bilateral adnexal masses Both with colour score 70 5/12 (41.7) d,f 1/2 e (50) 1/3 (33.3) 7/17 (41.2) One with colour score 70 3/12 (25) d,f 0/2 e 2/3 (77.8) 5/17 (29.4) None with colour score 70 4/12 (33.3) d,f 1/2 e (50) 0/3 5/17 (29.4) Results are shown as the median (range) or n (%). a Pelvic pain with unknown etiology (n ¼ 7), appendicitis (n ¼ 6), cervicitis (n ¼ 3), peritoneal endometriosis (n ¼ 2), ovarian cyst (n ¼ 2), adnexal torsion (n ¼ 2), urinary tract infection (n ¼ 2), Crohn s disease (n ¼ 1), cystadenocarcinoma of the appendix (n ¼ 1). b One woman in perimenopause (adnexal torsion) is not included in the calculations. c Polycystic appearance was defined as an ovary containing 10 follicles 2 10 mm in diameter. d The information on colour score was missing for the biggest mass in one patient with bilateral solid masses adjacent to the ovary. e The information on colour score was missing for both masses in one patient with bilateral solid masses adjacent to the ovary. f The information on colour score was missing for the smallest mass in one patient with bilateral multilocular-solid masses without a clearly discernable ovary. of bilateral adnexal masses with regard to moderate or severe salpingitis were 100% (13/13, 95% CI %) and 82% (32/39, 95% CI 67 91%) and the positive and negative likelihood ratios were 5.1 and 0.04, respectively. Ultrasound findings in patients with mild salpingitis (red, swollen tubes and pus or exudate from the tubal fimbriae provoked only by manipulation at laparoscopy) The only patient with mild salpingitis that was diagnosed with ultrasound had bilateral solid masses with diameters of 19 and 23 mm, respectively, lying adjacent to the ovary. The colour scores were 14 and 65, peak systolic velocities (PSVs) were 4 and 23 cm/s, TAMXV were 2 cm/s and 10 cm/s and PI were 1.60 and 2.03 in the smallest and largest masses, respectively. In the remaining three patients with mild salpingitis, no adnexal masses were seen with ultrasound. Ultrasound findings in patients with moderate salpingitis (red, swollen, fixed and closed tubes, pus present spontaneously at laparoscopy) Seven of the eight patients with moderate salpingitis had bilateral masses lying adjacent to the ovary, and the other patient had a mass lying adjacent to the ovary on one side and a mass with no discernable ovary on the other side. Ten of the 15 masses lying adjacent to the ovary were solid, 4 were unilocular cystic (sausage-shaped, thick-walled unilocular structure with echogenic fluid inside, no cogwheel sign, no incomplete septae) and 1 was multilocular solid (thickwalled roundish lesion filled with echogenic fluid, no cogwheel sign, no incomplete septae). The mass without a discernable ovary was solid. The size of the smallest mass lying adjacent to the ovary was median 18 mm (15 23) and that of the largest mass 28 mm (24 32). Median colour scores in the smallest and largest masses were 75 (45 99) and 92 (5 97), median PSVs were 17 cm/s (9 26) and 15 cm/s (8 47),

6 1574 Romosan et al. Table III Results of Doppler ultrasound examination of the uterus and uterine and tubal arteries. Final diagnosis... Salpingitis (n 5 17) Endometritis (n 5 9) Others a (n 5 26) Total (n 5 52)... Colour score Endometrium 20 (0 99) 51 (3 92) 19 (0 72) 22 (0 99) Myometrium 51 (8 98) 34 (19 89) 55 (8 93) 54 (8 98) Spectral Doppler results Right uterine artery PSV (cm/s) 61 (17 115) 40 (25 51) 51 (20 97) 51 (17 115) TAMX, cm/s 20 (6 46) 11 (4 19) 18 (8 50) 17 (4 50) PI 2.40 ( ) 3.00 ( ) 2.81 ( ) 2.74 ( ) Left uterine artery PSV (cm/s) 59 (34 127) 56 (37 60) 50 (17 168) 52 (17 168) TAMXV, cm/s 26 (7 50) 16 (7 20) 14 (5 53) 18 (5 53) PI 2.21 ( ) 2.67 ( ) 3.04 ( ) 2.66 ( ) Right tubal artery PSV (cm/s) 21 (5 57) 16 (10 37) 24 (5 46) 21 (5 57) TAMXV (cm/s) 11 (2 26) 7 (3 12) 8 (2 65) 8 (2 65) PI 1.71 ( ) 1.98 ( ) 2.08 ( ) 2.04 ( ) Left tubal artery PSV (cm/s) 27 (5 49) 26 (6 36) 18 (7 35) 21(5 49) TAMXV (cm/s) 13 (3 26) 6 (2 15) 7 (2 18) 7 (2 26) PI 1.40 ( ) 2.65 ( ) 2.51( ) 2.29 ( ) Results are shown as the median (range). PSV, peak systolic velocity; TAMXV, time averaged maximum velocity; PI, pulsatility index. a Pelvic pain with unknown etiology (n ¼ 7), appendicitis (n ¼ 6), cervicitis (n ¼ 3), peritoneal endometriosis (n ¼ 2), ovarian cyst (n ¼ 2), adnexal torsion (n ¼ 2), urinary tract infection (n ¼ 2), Crohn s disease (n ¼ 1) and cystadenocarcinoma of the appendix (n ¼ 1). median TAMXV were 9 cm/s (5 16) and 9 cm/s (4 27) and median PI were 1.15 ( ) and 1.16 ( ). The mass without a discernable ovary measured 60 mm, had a colour score of 18, a PSV of 17 cm/s, a TAMXV of 12 cm/s and a PI of Ultrasound images from patients with laparoscopically confirmed moderate salpingitis are shown in Figs 1 3. Ultrasound findings in patients with severe salpingitis (pyosalpinx at laparoscopy) Three of the five patients with severe salpingitis had bilateral masses lying adjacent to the ovary: three of the six masses were solid and the other three were roundish or elongated multilocular thick-walled cystic structures containing echogenic fluid without cogwheel sign or incomplete septae. Two patients had bilateral adnexal masses without a discernable ovary: two were solid masses and two were multilocular-solid masses with thick walls and septae and with cyst locules containing homogenously echogenic fluid or fluid with echogenicity similar to what is seen in haemorrhagic corpora lutea (Valentin, 2004). Neither cogwheel sign nor incomplete septae were seen. The median sizes of the smallest and largest adnexal masses lying adjacent to the ovary were 21 (19 30) and 33 (27 46) mm, the median colour scores were 87 (29 95) and 76 (56 97), the median PSVs were 20 cm/s (12 21) and 14 cm/s (13 37), the median TAMXV were 8 cm/s (7 14) and 6 cm/s (6 22) and the median PI were 0.98 ( ) and 2.06 ( ), respectively. The median diameter of the smallest mass without a discernable ovary was 32 mm (30 34) and that of the largest was 48 (40 60) mm. The median colour scores were 71 and 73 (65 81), the median PSVs were 35 and 30 cm/s (18 41), the median TAMXV were 10 and 15 cm/s (8 21) and the median PI were 3.22 and 1.68 ( ) (velocimetry results were missing for one of the smallest masses), respectively. Ultrasound findings in patients with endometritis In six (66.6%) of the nine patients with a final diagnosis of endometritis, no adnexal masses were seen at ultrasound examination, while bilateral solid masses lying adjacent to the ovary were described in three patients. The median size of the smallest of the bilateral masses was 16 mm (15 16) and that of the largest was 19 mm (16 23). The colour content of the masses lying adjacent to the ovary in women with endometritis was lower than in patients with confirmed salpingitis, while the PI values were higher; the median colour scores in the smallest and largest masses in patients with endometritis being 51 (20 81) and 54 (20 88) and the median PI being 1.63 ( ) and 1.31 ( ). PSV and TAMXV in masses lying adjacent

7 Ultrasound for diagnosing acute salpingitis 1575 Table IV Diagnoses suggested by the ultrasound examiner on the basis of subjective evaluation of ultrasound findings. True diagnosis... Ultrasound Salpingitis Endometritis Others diagnosis (n 5 17) (n 5 9) (n 5 26)... Salpingitis a Appendicitis b Normal c ultrasound findings No diagnosis suggested d Ovarian cyst e Adnexal mass of unclear origin f a Final diagnosis was pain of unknown etiology (n ¼ 2), cervicitis (n ¼ 1) and appendicitis (n ¼ 1). b Final diagnosis was appendicitis (n ¼ 3) and peritoneal endometriosis (n ¼ 1). c Final diagnosis was pelvic pain of unknown etiology (n ¼ 4), cervicitis (n ¼ 2), urinary tract infection (n ¼ 2), appendicitis (n ¼ 1) and cystadenocarcinoma of the appendix (n ¼ 1). d Final diagnosis was pelvic pain of unknown etiology (n ¼ 1), appendicitis (n ¼ 1), Crohn s disease (n ¼ 1) and adnexal torsion (n ¼ 2); in one case of torsion, torsion of a diseased tube was one of the three possible diagnoses suggested by the ultrasound examiner. e Final diagnosis was ovarian cyst in both cases. f The final diagnosis was peritoneal endometriosis (no mass was confirmed at laparoscopy). to the ovary were similar in women with salpingits and endometritis, the median PSV and TAMVX in women with endometritis being 14 cm/s (8 16) and 6 cm/s (3 10) in the smallest mass and 14 cm/s (7 21) and 6 cm/s (3 13) in the largest mass. Ultrasound findings in patients with a final diagnosis other than salpingitis or endometritis In 15 of the 26 patients with a final diagnosis other than salpingitis or endometritis, no masses were detected at ultrasound examination. The final diagnosis in these 15 cases were pain of unknown etiology (n ¼ 4), cervicitis (n ¼ 3), appendicitis (n ¼ 3), urinary tract infection (n ¼ 2), peritoneal endometriosis (n ¼ 1), Crohn s disease (n ¼ 1) and cystadenocarcinoma of the appendix (n ¼ 1). In 2 of the 26 patients, unilateral ovarian lesions were seen at ultrasound examination and suggested by the ultrasound examiner to be a hemorrhagic corpus luteum cyst and a 50-mm bilocular ovarian cyst. The two diagnoses of ovarian cyst were confirmed at laparoscopy. A unilateral mass lying adjacent to the ovary was seen in 6 of the 26 patients. In one of these six cases, no mass was found at laparoscopy (the final diagnosis was pain of unknown etiology, and in retrospect the mass seen at ultrasound was probably a bowel loop). In four cases, the ultrasound image of the mass was judged to be compatible with acute appendicitis. This diagnosis was confirmed in three of the four cases. In the fourth case the appendix was judged to be normal at laparoscopy, and the final diagnosis was peritoneal endometriosis. In the last case, a multilocular-solid mass was suggested by the ultrasound examiner to be either torsion of a diseased tube, a pyosalpinx or, very unlikely, a malignancy. This mass was the only one manifesting the cogwheel sign (Fig. 4). The correct diagnosis was torsion of a hydrosalpinx. In 3 of the 26 patients, bilateral small diffusely delineated-solid masses lying adjacent to the ovary were seen at ultrasound examination. In two of these cases, the ultrasound examiner suggested a diagnosis of acute salpingitis, but no pathology was judged to be present at laparoscopy, and the final diagnosis was pain of unknown etiology (the sizes of the smallest masses were 15 and 26 mm, colour scores were 70 and 12, PSVs were 13 and 22 cm/s, TAMXV were 5 and 9 cm/s and PI were 1.88 and 1.75, while the sizes of the largest masses were 18 and 27 mm, colour scores were 95 and 87, PSVs were 8 and 13 cm/s, TAMXV were 4 and 8 cm/s and PI were 1.58 and 0.88, respectively). In the third case, torsion of a gangrenous hydatid of Morgagni was found at laparoscopy, while no mass was confirmed on the contralateral side. At ultrasound examination the mass corresponding to the hydatid of Morgagni was solid and had a size of 12 mm, a colour score of 22, PSV of 16 cm/s, TAMXV of 9 cm/s and PI of The mass that was not confirmed at laparoscopy was also considered to be solid, and had a size of 14 mm, a colour score of 70, PSV of 17 cm/s, TAMXV of 8 cm/s and PI of Discussion Our results showed that ultrasound findings suggestive of moderate or severe acute salpingitis were the presence of bilateral adnexal masses or the presence of bilateral masses lying adjacent to the ovary, with 100% (13 of 13) and 77% (10 of 13) of the patients with moderate-to-severe salpingitis confirmed by laparoscopy manifesting these signs compared with 25% (1 of 4) of the patients with mild salpingitis and 17% (6 of 35) of the patients with other diagnoses. Most masses lying adjacent to the ovaries in cases of salpingitis were solid, fewer were thick-walled elongated unilocular cystic masses or roundish or elongated multilocular or multilocular-solid masses containing echogenic fluid but not manifesting the cogwheel sign or incomplete septae. Most of these lesions were 2 3 cm in size and well vascularized at colour Doppler ultrasound examination. The strength of our study is that it contributes information to an area where scientific evidence is very scarce. To the best of our knowledge, the ultrasound findings in cases of mild or moderate salpingitis, but not distinguishing between the two, verified by laparoscopy have been described in only one publication. It includes six cases of mild or moderate salpingitis and shows ultrasound images of two of these cases (Molander et al., 2001). We are aware of only two published studies reporting on the sensitivity and specificity of ultrasound with regard to laparoscopically confirmed acute salpingitis (Tukeva et al., 1999; Molander et al., 2001). Both include mainly patients with pyosalpinx or tubo-ovarian abscess, and only one of them has a design appropriate for estimating sensitivity and specificity (Table V) (Tukeva et al., 1999). Details on published studies reporting on the sensitivity and specificity of ultrasound for diagnosing upper genital tract infection are shown in Table VI (Cacciatore et al., 1992; Boardman et al., 1997). Our study has limitations. First, the sample size is small. This is explained mainly by difficulties with patient recruitment (doctors in

8 1576 Romosan et al. Figure 1 Ultrasound images from one patient with moderate acute salpingitis verified by laparosocopy. (A) and (B) show gray scale ultrasound images of the left tube, (C) and (D) show colour Doppler images of the same tube. The lesion is a sausage-shaped thick-walled unilocular cystic structure with a very small amount of echogenic fluid inside. We interpret the white oval ring in (B) as the mucosa of the inflamed tube. As seen in (C) and (D), the tube is extremely well vascularized in Doppler ultrasound examination. Please note the ring of colour in (D). We interpret this as rich vascularisation surrounding a transverse section through the inflamed tube. We observed this finding also in other cases of moderate salpingitis, see Figs 2 and 3. Figure 2 Ultrasound images of moderate acute salpingitis verified by laparosocopy in a second patient. (A) A sausage-shaped solid structure corresponding to the inflamed tube. (B) The rich vascularisation of the same structure and rings of colour are discernable, see also Figs 1 and 3. the emergency ward forgetting to recruit patients, patients declining to undergo diagnostic laparoscopy). According to our hospital statistics, 245 patients had a diagnosis of acute salpingitis either as inpatients or outpatients in our hospital during the study period. Our study sample includes only 17 of these. Secondly, there were few cases of mild salpingitis in our study sample. This means that we cannot estimate with any precision the ability of ultrasound to detect very early salpingitis. Clearly, the proportion of cases with salpingitis of different grade affects the sensitivity and specificity of ultrasound, and the sensitivity and specificity that we report here are generalizable only to patient populations similar to our study population. Moreover, one can expect results similar to ours only if ultrasound is carried out by experienced ultrasound examiners using high-end ultrasound systems. The small number of patients with mild salpingitis may reflect either that doctors did not recommend laparoscopy to all patients fulfilling our eligibility criteria (which they should have done both according to the policy of our department and our study protocol), that a higher proportion of patients with mild salpingitis than moderate or severe salpingitis declined to participate in the study, or that few patients with mild salpingitis fulfilled our eligibility criteria. A third limitation, and one that we share with other studies trying to estimate the sensitivity and specificity of ultrasound with regard to

9 Ultrasound for diagnosing acute salpingitis 1577 Figure 3 Ultrasound images of moderate acute salpingitis verified by laparosocopy in a third patient. (A) A unilocular sausage-shaped thick-walled structure corresponding to the inflamed tube with a very small amount of echogenic fluid inside. (B) A transverse section through the same tube. (C) The rich vascularisation of the same tube. Please note the ring of colour surrounding the transverse section of the tube, see also Figs 1 and 2. Figure 4 Ultrasound images of a hydrosalpinx that has undergone torsion. This is a 3-cm multilocular solid mass lying adjacent to the ovary. Swollen mucosal folds protrude into the fluid-filled lumen of the mass. This is the only mass in our series manifesting the cogwheel sign. The ultrasound examiner suggested three possible diagnoses: torsion of a diseased tube, pyosalpinx, or, very unlikely, a malignancy. acute salpingitis, is the lack of an obvious gold standard. Salpingitis may be present in the absence of histological signs of endometritis (Sellors et al., 1991). In our opinion, the best gold standard is diagnostic laparoscopy. Still, diagnostic laparoscopy is not ideal. Sellors et al. (1991) found laparoscopy to have low sensitivity (58%) with regard to histologically confirmed salpingitis, and Molander et al. (2003) reported poor intra-and inter-observer agreement with regard to PID when six gynaecologists evaluated laparoscopic images of the female pelvis. The ultrasound image of early salpingitis has been described by Molander et al. (2001) as a solid mass with high colour content at power Doppler examination located close to the ovary. Our results agree fairly well. However, neither we nor Boardman et al. (1997) were able to confirm the findings of Cacciatore et al. (1992) that fluid in the pouch of Douglas and polycystic appearance of the ovaries are reliable signs of upper genital tract infection. Even though our results confirm that inflamed tubes are richly vascularized at Doppler examination (Tinkanen and Kujansuu, 1992; Alatas et al., 1996; Molander et al., 2001), all our Doppler results overlapped too much between patients with different diagnoses for them to be clinically useful. This is in accordance with the findings in the case control study by Molander et al. (2001) where ultrasound images of acute salpingitis (cases) were compared with those of hydrosalpinx (controls). Possibly, the inability of Doppler ultrasound to distinguish upper genital tract infections from other conditions in the pelvis is

10 1578 Romosan et al. Table V Summary of studies reporting the sensitivity and specificity of ultrasound in diagnosing salpingitis. Number of cases with peritonitis Number of cases with abscess Number of cases with salpingitis grade 3 (pyosalpinx) Sensitivity, % Specificity, % Number of cases with salpingitis grade 1 or 2 Study Design End-point Gold standard... Laparoscopy 81 (17/21) 78 (7/9) Salpingitis or abscess Prospective observational Tukeva et al. (1999) Laparoscopy 100 (20/20) 90 (18/20) 6 9 5? Case control a Salpingitis or abscess Molander et al. (2001) Salpingitis Laparoscopy 82 (14/17) 83 (29/35) Current Prospective study b observational a Controls were patients with hydrosalpinx. b Results presented for the current study are those for bilateral adnexal masses. explained by Doppler measurements not being sufficiently precise or accurate. Two studies (Tukeva et al., 1999; Molander et al., 2001) reported very high sensitivity and specificity of ultrasound for diagnosing PID. The higher sensitivity in these studies than in ours is likely to be explained by a much higher prevalence of pyosalpinx and tubo-ovarian abscess in the other studies (Table V). The sensitivity and specificity reported by Molander et al. (2001) are not applicable to patients with clinical signs of acute PID, because they calculated sensitivity using patients with laparoscopically confirmed PID (cases) and specificity using patients with hydrosalpinx (control group). Our finding that 44% (23/52) of the patients with clinical signs of PID had normal laparoscopy findings or a final diagnosis unrelated to PID agrees with those of others, the corresponding figures in other studies being 30% (9/30) (Tukeva et al., 1999), 35% (282/814) (Jacobson and Westrom, 1969), 39% (13/33) (Molander et al., 2000) and 33% (10/30) (Molander et al., 2001). In our study as well as in others, common diagnoses unrelated to PID in patients with clinical signs of PID were appendicitis (Jacobson and Westrom, 1969; Molander et al., 2000) adnexal torsion (Tukeva et al., 1999; Molander et al., 2000), ovarian cysts (Jacobson and Westrom, 1969; Tukeva et al., 1999; Molander et al., 2000) and endometriosis (Jacobson and Westrom, 1969; Tukeva et al., 1999; Molander et al., 2000). Our results support that ultrasound is likely to be helpful when managing patients with symptoms and clinical signs of acute PID, because symptoms and signs of PID overlap with those of several diagnoses unrelated to genital infection. Ultrasound signs of affected tubes changed the odds of salpingitis only moderately (about five times) (Jaeschke et al., 1994), but even a small change in odds may be helpful in patients presenting a diagnostic dilemma (Jaeschke et al., 1994). Moreover, in the absence of bilateral adnexal masses, the odds of moderate or severe salpingitis decreased.20-fold, while mild salpingitis could not be excluded. This information provided by transvaginal ultrasound is likely to be of help when deciding on whether or not to proceed with diagnostic laparoscopy in patients with symptoms and signs suggesting PID and, if laparoscopy is not performed, for selecting treatment and planning follow-up. In addition, ultrasound may reveal diagnoses unrelated to PID, e.g. appendicitis, ovarian cysts including endometriomas and torsion of the adnexa. Authors roles G.R. recruited patients, performed the statistical analysis, drafted the manuscript and approved the final version submitted for publication. C.B. recruited patients, revised the manuscript critically for important intellectual content and approved the final version submitted for publication. L.S. examined all endometrial biopsies, revised the manuscript critically for important intellectual content and approved the final version submitted for publication. L.V. designed the study, performed all the ultrasound examinations, participated in the statistical analysis and interpretation of the results, revised the manuscript critically for important intellectual content and approved the final version submitted for publication.

11 Ultrasound for diagnosing acute salpingitis 1579 Table VI Summary of studies reporting the sensitivity and specificity of ultrasound in diagnosing upper genital tract infection. Study Design End-point Gold standard Sensitivity, % Specificity, % Number of cases with salpingitis grade 1 or 2, pyosalpinx or abscess... Cacciatore Prospective Plasma cell Endometrial 85 (11/13) 100 (38/38)? et al. (1992) observational endometritis histology Boardman et al. (1997) Prospective observational Upper genital tract infection Laparoscopy (n ¼ 28) or Endometrial histology and/or Microbiology (n ¼ 27) 32 (6/19) 97 (35/36)? Funding This work was supported by funds administered by Malmö University Hospital; and two Swedish government grants (ALF-medel and Landstingsfinansierad Regional Forskning). Conflict of interest None declared. References Alatas C, Aksoy E, Akarsu C, Yakin K, Bahceci M. Hemodynamic assessment in pelvic inflammatory disease by transvaginal color Doppler ultrasonography. Eur J Obstet Gynecol Reprod Biol 1996;70: Blaustein A, Kurman RJ. Blaustein s Pathology of the Female Genital Tract, 5th edn. New York: Springer, Boardman LA, Peipert JF, Brody JM, Cooper AS, Sung J. Endovaginal sonography for the diagnosis of upper genital tract infection. Obstet Gynecol 1997;90: Cacciatore B, Leminen A, Ingman-Friberg S, Ylostalo P, Paavonen J. Transvaginal sonographic findings in ambulatory patients with suspected pelvic inflammatory disease. Obstet Gynecol 1992;80: CDC. Sexually Transmitted Diseases Treatment Guidelines. Centers for Disease Control and Prevention, 2010, std/treatment/2010/std-treatment-2010-rr5912.pdf (1 March 2013, date last accessed). Hager WD, Eschenbach DA, Spence MR, Sweet RL. Criteria for diagnosis and grading of salpingitis. Obstet Gynecol 1983;61: Jacobson L, Westrom L. Objectivized diagnosis of acute pelvic inflammatory disease. Diagnostic and prognostic value of routine laparoscopy. Am J Obstet Gynecol 1969;105: Jaeschke R, Guyatt GH, Sackett DL. Users guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group. JAMA 1994;271: Kirchler HC, Kolle D, Schwegel P. Changes in tubal blood flow in evaluating ectopic pregnancy. Ultrasound Obstet Gynecol 1992;2: Molander P, Cacciatore B, Sjoberg J, Paavonen J. Laparoscopic management of suspected acute pelvic inflammatory disease. J Am Assoc Gynecol Laparosc 2000;7: Molander P, Sjoberg J, Paavonen J, Cacciatore B. Transvaginal power Doppler findings in laparoscopically proven acute pelvic inflammatory disease. Ultrasound Obstet Gynecol 2001;17: Molander P, Finne P, Sjoberg J, Sellors J, Paavonen J. Observer agreement with laparoscopic diagnosis of pelvic inflammatory disease using photographs. Obstet Gynecol 2003;101: Okaro E, Valentin L. The role of ultrasound in the management of women with acute and chronic pelvic pain. Best Pract Res Clin Obstet Gynaecol 2004;18: Sellors J, Mahony J, Goldsmith C, Rath D, Mander R, Hunter B, Taylor C, Groves D, Richardson H, Chernesky M. The accuracy of clinical findings and laparoscopy in pelvic inflammatory disease. Am J Obstet Gynecol 1991;164: Timmerman D, Valentin L, Bourne TH, Collins WP, Verrelst H, Vergote I. Terms, definitions and measurements to describe the sonographic features of adnexal tumors: a consensus opinion from the International Ovarian Tumor Analysis (IOTA) Group. Ultrasound Obstet Gynecol 2000;16: Timor-Tritsch IE, Lerner JP, Monteagudo A, Murphy KE, Heller DS. Transvaginal sonographic markers of tubal inflammatory disease. Ultrasound Obstet Gynecol 1998;12: Tinkanen H, Kujansuu E. Doppler ultrasound studies in pelvic inflammatory disease. Gynecol Obstet Invest 1992;34: Tukeva TA, Aronen HJ, Karjalainen PT, Molander P, Paavonen T, Paavonen J. MR imaging in pelvic inflammatory disease: comparison with laparoscopy and US. Radiology 1999;210: Valentin L. Pattern recognition of pelvic masses by gray-scale ultrasound imaging: the contribution of Doppler ultrasound. Ultrasound Obstet Gynecol 1999;14: Valentin L. Use of morphology to characterize and manage common adnexal masses. Best Pract Res Clin Obstet Gynaecol 2004; 18: Valentin L, Sladkevicius P, Marsal K. Limited contribution of Doppler velocimetry to the differential diagnosis of extrauterine pelvic tumors. Obstet Gynecol 1994;83: